Mechanisms of stem cell homeostasis during C. elegans germline development

Established: October 1, 2012

The establishment of homeostasis between cell growth, differentiation and apoptosis is of key importance for organogenesis. Stem cells respond to temporally and spatially regulated signals by switching from mitotic proliferation to asymmetric cell division and differentiation. Executable computer models of signalling pathways can accurately reproduce a wide range of biological phenomena by reducing detailed chemical kinetics to a discrete, finite form. Moreover, coordinated cell movements and physical cell-cell interactions are required for the formation of three-dimensional structures that are the building blocks of organs. To capture all these aspects, we are developing a hybrid executable and physical model describing stem cell proliferation, differentiation and homeostasis in the Caenorhabditis elegans germline. Using this hybrid model, we aim to track cell lineages and dynamic cell movements during germ cell differentiation in order to better understand how apoptosis regulates germ cell homeostasis in the gonad, and identify potential mechanisms to ensure stable fate patterns. In collaboration with Ben Hall (MRC Cancer Unit, University of Cambridge).